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    INHIBITION OF REPERFUSION INJURY WITH A PSD-95 INHIBITOR
    2.
    发明公开
    INHIBITION OF REPERFUSION INJURY WITH A PSD-95 INHIBITOR 审中-公开

    公开(公告)号：US20230285504A1

    公开(公告)日：2023-09-14

    申请号：US17800883

    申请日：2021-02-19

    申请人： NONO INC.

    发明人： Michael TYMIANSKI

    IPC分类号： A61K38/10 ,  A61K38/48 ,  A61P25/28 ,  A61P7/02 ,  A61P9/10

    CPC分类号： A61K38/10 ,  A61K38/482 ,  A61P25/28 ,  A61P7/02 ,  A61P9/10

    摘要： The peptide inhibitor of PSD-95, Tat-NR2B9c, and related peptides can inhibit reperfusion injury when administered before blood flow is restored. This role is in addition to the role of active agent that inhibits PSD-95 inhibiting damage resulting from ischemia and resulting excitotoxicity. The relative timing of administering an active agent that inhibits PSD-95 and reperfusion by thrombolytic agents is additionally influenced by degradation of plasmin-sensitive active agent that inhibits PSD-95 by plasmin induced by thrombolytic agents if the active agent that inhibits PSD-95 and plasmin are co-resident in the plasma. Plasmin-degradation can be reduced or avoided and the benefit of inhibiting reperfusion injury obtained by administering an active agent that inhibits PSD-95 before restoration of blood flow by reperfusion, preferably at least 10, 15, 20, 22, 25, 30, 40, 50 or 60 minutes before restoration of blood flow by reperfusion.

    Therapy for subarachnoid hemorrhage and ischemia
    3.
    发明授权
    Therapy for subarachnoid hemorrhage and ischemia 有权

    公开(公告)号：US11338015B2

    公开(公告)日：2022-05-24

    申请号：US16381757

    申请日：2019-04-11

    申请人： NoNO, Inc.

    发明人： Michael Tymianski

    IPC分类号： A61K38/16 ,  A61K38/10 ,  A61K45/06 ,  A61K49/00 ,  A61K38/08 ,  G01N33/68 ,  C07K14/705 ,  C07K14/47 ,  C12N7/00 ,  A61K38/00

    摘要： The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefitting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

    Combination therapy for ischemia
    4.
    发明授权
    Combination therapy for ischemia 有权

    公开(公告)号：US10967041B2

    公开(公告)日：2021-04-06

    申请号：US16051971

    申请日：2018-08-01

    申请人： NONO INC.

    发明人： Michael Tymianski

    IPC分类号： A61K38/10 ,  A61K38/49 ,  A61K38/17

    摘要： The invention provides a combination treatment for ischemia conditions in or otherwise affecting the CNS, such as stroke. The treatment involves administration of a PSD-95 inhibitor and performing reperfusion therapy (e.g., by administration of tPA). Administering a PSD-95 inhibitor in combination with reperfusion therapy increases the efficacy of the reperfusion therapy and/or slows the decline in efficacy of reperfusion therapy with time after onset of ischemia thus extending the window in which reperfusion therapy can be administered.

    Therapy for subarachnoid hemorrhage and ischemia
    5.
    发明授权
    Therapy for subarachnoid hemorrhage and ischemia 有权

    公开(公告)号：US10300110B2

    公开(公告)日：2019-05-28

    申请号：US14965694

    申请日：2015-12-10

    申请人： NoNO Inc.

    发明人： Michael Tymianski ,  Jonathan David Garman

    IPC分类号： G01N33/68 ,  A61K38/16 ,  A61K38/10 ,  A61K45/06 ,  A61K49/00 ,  A61K38/08 ,  C07K14/705 ,  C07K14/47 ,  C12N7/00 ,  A61K38/00

    摘要： The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefiting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

    Co-Administration of An Agent Linked to an Internalization Peptide With an Anti-Inflammatory
    9.
    发明申请
    Co-Administration of An Agent Linked to an Internalization Peptide With an Anti-Inflammatory 有权
    与具有抗炎症的内化肽相关联的试剂的共同管理

    公开(公告)号：US20120252731A1

    公开(公告)日：2012-10-04

    申请号：US13377519

    申请日：2010-06-10

    申请人： Michael Tymianksi ,  Jonathan David Garman

    发明人： Michael Tymianksi ,  Jonathan David Garman

    IPC分类号： A61K38/10 ,  A61P29/00 ,  C07K7/08 ,  A61P37/08 ,  A61K38/00 ,  A61K38/08

    CPC分类号： A61K47/64 ,  A61K31/275 ,  A61K31/277 ,  A61K38/08 ,  A61K38/10 ,  A61K45/06 ,  A61K47/645 ,  C07K16/1072 ,  C07K2319/10 ,  A61K2300/00

    摘要： The invention provides methods of delivering pharmacologic agents linked to an internalization peptide, in which an inflammatory response inducible by the internalization peptide is inhibited by co-administration of an anti-inflammatory or by linking the internalization peptide to biotin or similar molecule. Such methods are premised in part on the results described in the examples whereby administration of a pharmacological agent linked to tat at high dosages is closely followed by an inflammatory response, which includes mast cell degranulation, histamine release and the typical sequelae of histamine release, such as redness, heat, swelling, and hypotension.

    摘要翻译： 本发明提供了递送与内化肽连接的药理学试剂的方法，其中通过共同给予抗炎剂或通过将内化肽与生物素或类似分子连接来抑制内化肽诱导的炎症反应。 这些方法部分地基于实施例中描述的结果，其中以高剂量施用与tat连接的药剂紧随其后是炎性反应，其包括肥大细胞脱粒，组胺释放和组胺释放的典型后遗症，例如 作为发红，发热，肿胀和低血压。

    Combination therapy for ischemia
    10.
    发明授权
    Combination therapy for ischemia 有权

    公开(公告)号：US11878044B2

    公开(公告)日：2024-01-23

    申请号：US17177970

    申请日：2021-02-17

    申请人： NoNO Inc.

    发明人： Michael Tymianski

    IPC分类号： A61K38/10 ,  A61K38/49 ,  A61K38/17

    CPC分类号： A61K38/10 ,  A61K38/1787 ,  A61K38/49 ,  A61K38/1787 ,  A61K2300/00 ,  A61K38/49 ,  A61K2300/00

    摘要： The invention provides a combination treatment for ischemia conditions in or otherwise affecting the CNS, such as stroke. The treatment involves administration of a PSD-95 inhibitor and performing reperfusion therapy (e.g., by administration of tPA). Administering a PSD-95 inhibitor in combination with reperfusion therapy increases the efficacy of the reperfusion therapy and/or slows the decline in efficacy of reperfusion therapy with time after onset of ischemia thus extending the window in which reperfusion therapy can be administered.